Background: Uncontrolled diabetes mellitus plays a significant role in the development of diabetic nephropathy. Aim: This study was performed to assess the pathological effect of diabetes on the kidney, the possible improvement of diabetic nephropathy by Insulin, and the therapeutic effect of mesenchymal stem cells. Methods: 50 healthy albino adult male rats s were subdivided into two main groups, Group 1: control group. Group 2: 42 rats were given a single intraperitoneal injection of streptozotocin (80 mg/kg). After 6 weeks, confirming diabetic nephropathy, rats were dispersed into 3 groups as follows; Group( 2a): diabetic nephropathic untreated rats, Group (2b) was given insulin glargine 6 IU/24 hours, for 6 weeks and Group (2c) was received MSCs in intravenous injection (106 cells) per rat once. After sacrificing rats at the end of the experiment, blood sampling was done for laboratory analysis of serum urea, and creatinine. Kidney samples were prepared for light and electron microscopic examination. Results: Diabetic rats showed altered biochemical and histological changes which dilated filtration space, focal lytic areas, and congested blood capillaries were observed in the diabetic group. Disfigurement of the renal tubules, with vacuolated cytoplasm in the insulin group while, normal appearance with mild increase in the Bowman's space in the MSCs group, with significant ameliorative effects on renal function. Conclusion: Treatment with insulin and MSCs showed improved histological and biochemical parameters in the kidneys of diabetic rats.